PROJECT SUMMARY Chronic digestive illness affecting the esophagus, including gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), achalasia and functional dysphagia are common and pose a significant economic burden. These are heterogeneous conditions whose pathophysiology occurs on a wide spectrum based on degree of abnormal acid exposure, motor dysfunction, bolus retention and degree of esophageal hypersensitivity. Symptom-to-physiology correlations are poor, indicating that other processes influence symptom experience. Almost half of patients continue to experience symptoms despite first-line treatments, leaving these patients with inadequate treatment options. There is a need for more personalized interventions targeting the bolus transit system that operate subconsciously to suppress the perception of bolus transit and muscle contraction. Centrally-mediated psychological processes such as esophageal hypervigilance, catastrophizing, and visceral hypersensitivity drive symptom experience, independent of acid exposure, motility function, or eosinophilia histology. Autonomic nervous system (ANS) arousal, the physiological ?fight-or-flight? response to fear and hypervigilance, perpetuates these psychological processes. Heart rate variability (HRV), or the variation in time intervals between heart beats, serves as a biomarker for overall ANS functioning. Higher HRV is indicative of a greater ability to adapt to stressful situations, such as when experiencing esophageal symptoms. A less studied, yet important construct is cognitive flexibility, or the ability to appropriately shift thoughts and adapt behavior. Cognitive flexibility is a modifiable construct that if improved through training, can improve outcomes and prepare patients for behavioral treatments who may otherwise be poor responders. We aim to characterize the degree of cognitive flexibility in well-defined patient populations based on mechanical and physiological phenotypes derived from our biophysiologic modeling CORE. Then, we aim to evaluate heart rate variability biofeedback (HRVB), a novel intervention for these four patient groups. Patients will be stratified by cognitive flexibility level, with those identified as low undergoing Cognitive Remediation Therapy (CRT), a brief intervention using cognitive exercises to improve thinking strategies. We hypothesize applying HRVB to target ANS arousal in real-time, as the symptoms are being experienced, will be effective in increasing HRV, decreasing symptoms, and improving quality of life. We also expect HRVB will decrease esophageal hypervigilance in comparison to controls. We hypothesize CRT will be a feasible and acceptable intervention for esophageal patients, and will be associated with positive changes in cognitive flexibility, decreased symptoms, and improved quality of life. Finally, we aim to develop an integrative predictive model using biomarkers of esophageal distensibility, measures of HRV and measures of cognitive flexibility to define management and outcomes. The results will have implications for current and future behavioral interventions for individuals with chronic esophageal disorders.